Vitamin A deficiency has been reported frequently among children in all parts of the world and some of its metabolic effects have been described, although limited information is available with regard to mineralized tissues such as bone and teeth. Data obtained in studies sponsored by this grant indicated an important role of vitamin A in the metabolism of sulfated glycosaminoglycans, the morphologic integrity of dentin and the dental caries susceptibility of rat molars when the deficiency was imposed during the time of rat molar mineralization. We propose to investigate these new findings using improved methodology and approaches which include the use of synchronous vitamin A deficient rat and a special programmed feeder to regulate the diet intake of control pair fed animals. With this animal model system and organ culture methods, we propose to examine the biochemical and morphologic events taking place in dentin when vitamin A deficiency is allowed to develop in laboratory rats. Specifically, we are interested in: a) the structural and biochemical events that lead to odontoblast differentiation and normal function, b) the biochemistry of dentin proteoglycans and glycosaminoglycans, c) the correlation of the vitamin A deficiency effect on dentin observed in incisors with those seen in molars, that could account for the increased caries susceptibility of the latter, and d) evaluation of possible neutralization affects of some analogs of vitamin A on the increased caries susceptibility induced by vitamin A deficiency. The initial hypothesis of this proposal remains that vitamin A is essential to proper calcification of bone and dentin, and research efforts will be concentrated in elucidating the cellular and biochemical events that mark this nutritional influence. of vitamin A on mineralized tissues.